The present invention relates to an implant according to the preamble of claim 1.
Here, the term xe2x80x9cimplantxe2x80x9d is to be first understood in a narrower sense as an element to be inserted at least temporarily in the body of an animal or a human, which, for example, can exclusively exercise therapeutic functions, but can also exercise support and/or joint functions. In a broader sense, however, elements which can be brought into contact with the body externally, particularly temporarily, or the like are also meant here.
The term xe2x80x9ctherapeutic agentxe2x80x9d here particularly refers to drugs and/or pharmaceuticals on one hand and medications and other substances to be supplied to the human or animal body on the other hand. In particular, all of the therapeutic agents mentioned in EP-A-0 875 218 as xe2x80x9cmedicationsxe2x80x9d and/or receptor agonists, receptor antagonists, enzyme inhibitors, neurotransmitters, cytostatics, antibiotics, hormones, vitamins, metabolic substrates, anti-metabolites, diuretics, and the like can be considered a therapeutic agent.
An implantable infusion pump is known from DE-C-197 04 497, which represents the most relevant prior art, in which a drug is driven out of a receptacle space by means of a propellant and released into the body via a catheter. A throttle path is provided between the receptacle space and the catheter. The throttle path is formed by a perfusion plate which is provided with multiple bores of a magnitude of 1 xcexcm. The bores are made in the perfusion plate by means of a laser beam, the perfusion plate consisting of ceramic, for example.
The drug flows through the bores of the perfusion plate into the adjacent catheter due to the pressure produced by the propellant in the known infusion pump. In this case, the perfusion plate acts as a throttle point, i.e. the amount of drug flowing through per unit of time depends on the pressure of the propellant and the fluidic properties of the drug. During this flow through the perfusion plate, the interaction between the bores of the perfusion plate and the drug expelled is restricted to the throttle effect of the bores, i.e. to a quasi-mechanical influence relative to the flow. It is hereby disadvantageous that the amount of drug released and/or flowing through per unit of time depends on the pressure produced by the propellant, so that unavoidable pressure changes often lead to undesired oscillations of the release speed. Another disadvantage is that the bores of the perfusion plate or other throttles can at least partially clog due to deposition of substances penetrating them. This leads to an undesired and undefined change of the throttle effect and thereby to an undesired influence on the amount of drug released and/or flowing through per unit of time.
The object of the present invention is to provide an implant which, particularly even for the smallest of quantities, allows preferably pressure-independent release per unit of time of a therapeutic agent and/or at least one active substance of the therapeutic agent, wherein, in particular, the problem of deposition of materials can be prevented, at least as much as possible.
The above object is achieved by an implant according to claim 1. Advantageous embodiments are objects of the subclaims.
A fundamental idea of the present invention is to provide a diffusion element with open pores, so that only diffusion is allowed, but not free flow and/or to provide a chemical modification of pore walls so that an interaction, which is preferably selective in regard to passage, can be achieved with a therapeutic agent and/or at least one active substance of the therapeutic agent. Thus, a released amount per unit of time can be reached which is at least largely independent from the pressure acting on the therapeutic agent. As a consequence, a more exact dosing is possible, particularly for small released amounts. Furthermore, clogging and/or blockage of the permeable element is prevented, at least as much as possible, in the embodiment according to the invention.
According to a preferred embodiment, the pores of the permeable element have, on average, a diameter of 20 nm to 250 nm. Free flow through the pores is prevented, at least as much as possible by this pore size, so that the desired independence from pressure of the released amount per unit of time occurs. In addition, this pore size prevents the entrance of bodily substances, such as proteins, into the pores and therefore into the implant.
The walls of the pores of the permeable element can, for example, be implemented as hydrophilic or hydrophobic and/or be provided, at least partially, with functional groups for chemical modification. Thus, it is possible that, e.g. only the therapeutic agent or only one active substance of the therapeutic agent can pass through the pores, so that selective interaction between the chemically modified pore walls and the therapeutic agent and/or at least one active substance of the therapeutic agent can be achieved. This selective interaction can prevent undesired clogging and/or blockage of the pores.
The permeable element of the proposed implant is preferably produced essentially from metal oxide and/or ceramic material. Very simple production and formation of highly uniform pores in the permeable element is made possible preferably by an artificial, particularly electrolytic, oxidation (anodization), particularly of aluminum. In principle, all so-called valve metal oxides are suitable for this purpose, such as aluminum oxide, tantalum oxide, iron oxide, tungsten oxide, and/or titanium oxide, as well as magnesium oxide.
The diameter of the pores and the surface density of the pores, i.e. the number of pores per area, can be varied by varying the electrical voltage during anodization. As a consequence, the shape of the pores can be controlled within wide ranges. In particular, the pores are, at least essentially, formed as tubes and extend from the surface of the permeable element essentially perpendicularly through the permeable element, wherein the cross-section of the pores and/or their openings can be portionally reduced with respect to diameter and/or area in order to achieve desired characteristics.
A particularly preferred embodiment is characterized by a second passage opening associated with the receptacle space, in which a permeable element/membrane-like separating element is inserted as well, so that the therapeutic agent or at least one active substance of the therapeutic agent can leave the receptacle space through the one opening/the permeable element inserted in the opening and substances can enter into the receptacle space from outside through the other passage opening/the permeable or separating element inserted in the permeable element. This quasi-double osmosis can be achieved by desired, different formation and/or chemical modification of the permeable elements. The substances, such as water or the like, penetrating from the outside into the receptacle space can compensate for a reduction in volume of the therapeutic agent in the receptacle space, so that neither low pressure, interfering with the release of the therapeutic agent from the receptacle space nor a pressure difference destroying the permeable element can occur.
If necessary, a wall element can be provided to divide the receptacle space, in order to prevent mixing and/or dilution of the therapeutic agent by the substances penetrating into the receptacle space.